Gridless, focusing ion extraction device for a time-of-flight mass spectrometer

ABSTRACT

A miniature time-of-flight mass spectrometer (TOF-MS) is provided having (1) a gridless, focusing ionization extraction device allowing for the use of very high extraction energies in a maintenance-free design, (2) a miniature flexible circuit-board reflector using rolled flexible circuit-board material, and (3) a low-noise, center-hole microchannel plate detector assembly that significantly reduces the noise (or “ringing”) inherent in the coaxial design. A method is also provided for increasing the collection efficiency of laser-desorbed ions in the TOF-MS. The method includes the steps of providing within the TOF-MS an ionization extraction device having an unobstructed central chamber having a first region and a second region; creating an ion acceleration/extraction field within the first region; accelerating ions within the first region; de-accelerating the ions in the second region; and drifting the ions in a drift region to cause ion dispersion.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of prior filed co-pendingU.S. Provisional Patent Application No. 60/203,595, filed May 12, 2000.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to a miniature time-of-flight massspectrometer (TOF-MS). The inventive spectrometer includes (1) agridless, focusing ionization extraction device allowing for the use ofvery high extraction energies in a maintenance-free design, and (2) alow-noise, center-hole microchannel plate detector assembly thatsignificantly reduces the noise (or “ringing”) inherent in the coaxialdesign.

[0004] 2. Description of the Related Art

[0005] Miniature time-of-flight mass spectrometers (TOF-MS) have thepotential to be used in numerous field-portable and remote samplingapplications due to their inherent simplicity and potential forruggedization. Conventional wisdom, however, holds that a compact TOF-MSwould not have sufficient drift length to achieve high performance, asmeasured by good resolving power or the capability to detect andidentify product ions.

[0006] These capabilities, found only in laboratory grade instruments,would greatly enhance the utility of a field portable TOF-MS. Withoutthe benefit of an extended drift region (and thereby long flight times),good resolution can only be achieved in a compact TOF-MS if the ionpeaks are quite narrow. All aspects of the miniature analyzer andionization processes that affect ion peak widths must therefore beoptimized for minimum peak broadening to improve the overall performanceof the field portable TOF-MS.

[0007] Commercially available short-pulse lasers and fast transientdigitizers enable the creation and measurement of very narrow ionsignals, but the ion source region, reflector performance, and detectorresponse will each contribute to the final peak width as well. To thisend, components need to be developed for the miniature TOF-MS thatimprove its overall performance.

[0008] Accordingly, a need exists to develop components for theminiature TOF-MS that improve its overall performance and are compatiblewith short-pulse lasers and fast transient digitizers. Morespecifically, a need exists for a focusing ionization extraction deviceand a low-noise channel-plate detector assembly which improve theoverall performance of the miniature TOF-MS.

SUMMARY OF THE INVENTION

[0009] The present invention provides a miniature time-of-flight massspectrometer (TOF-MS) having (1) a gridless, focusing ionizationextraction device allowing for the use of very high extraction energiesin a maintenance-free design, (2) a miniature flexible circuit-boardreflector using rolled flexible circuit-board material, and (3) alow-noise, center-hole microchannel plate detector assembly thatsignificantly reduces the noise (or “ringing”) inherent in the coaxialdesign. The components described herein improve the overall performanceof the TOF-MS. These components have been developed with specialattention paid to ruggedness and durability for operation of the TOF-MSunder remote and harsh environmental conditions.

[0010] The present invention also provides a method for increasing thecollection efficiency of laser-desorbed ions in the TOF-MS. The methodincludes the steps of A method for increasing the collection efficiencyof laser-desorbed ions in a TOF-MS, said method comprising the steps ofproviding an ionization extraction device within the TOF-MS, where theionization extraction device has an unobstructed central chamber havinga first region and a second region; creating an ionacceleration/extraction field within the first region; accelerating ionswithin the first region; de-accelerating the ions in the second region;and drifting the ions in a drift region to cause ion dispersion.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011]FIG. 1A is a cross-sectional view of a gridless, focusingionization extraction device for a TOF-MS according to the presentinvention;

[0012]FIG. 1B is a potential energy plot of the electric field generatedby the gridless, focusing ionization extraction device;

[0013]FIG. 2A is a perspective view of a flexible circuit-boardreflector in a rolled form according to the present invention;

[0014]FIG. 2B is top view of the flexible circuit-board reflector in anunrolled form;

[0015]FIG. 3A is a perspective view of a center-hole microchannel platedetector assembly according to the present invention;

[0016]FIG. 3B is a cross-sectional, exploded view of the center-holemicrochannel plate detector assembly showing the internal components;

[0017]FIG. 4 illustrates the detector response waveform for both thesingle ion signal from a conventional disk anode detector assembly andthe center-hole microchannel plate detector assembly having a pin anode;

[0018]FIG. 5 is a cut-away view of the TOF-MS having the gridless,focusing ionization extraction device, the flexible circuit-boardreflector and the center-hole microchannel plate detector assemblyaccording to the present invention; and

[0019]FIGS. 6A and 6B are spectra from solder foil and angiotensin IIcollected using the TOF-MS having the inventive components.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] A discussion is first made as to the inventive components of aminiature time-of-flight mass spectrometer (TOF-MS) of the presentinvention. The inventive components include (1) the gridless, focusingionization extraction device, (2) the flexible, circuit-board reflector,and (3) the center-hole microchannel plate detector assembly. Followingthis discussion, a description is provided of an experimental TOF-MSwhich was constructed and used to evaluate the performance of theinventive components.

[0021] I. Instrumentation

[0022] A. Gridless, Focusing Ionization Extraction Device

[0023] To increase the collection efficiency of laser-desorbed ions froma surface, a gridless focusing ionization extraction device of thepresent invention will now be described. The ionization extractiondevice is shown by FIG. 1A and designated generally by reference numeral100. The device 100 has a preferred length of approximately 17-25 mm andincludes a series of closely spaced micro-cylinders 110 a-c mountedwithin an unobstructed central chamber 105 which is defined by thehousing 115. The housing is constructed from one or more insulatingmaterials, such as ceramics, Teflon, and plastics, preferably, PEEKplastic.

[0024] The micro-cylinders 110 a-c are constructed from metallicmaterials, such as stainless steel and may have varying thicknessranges. Further, it is contemplated that each micro-cylinder isconstructed from a different metal and that each micro-cylinder has adifferent thickness. The micro-cylinders 110 create an extremely highion acceleration/extraction field (up to 10 kV/mm) in region 120, asshown by the potential energy plot depicted by FIG. 1B, between a flatsample probe 130 and an extraction micro-cylinder 110 a.

[0025] Ions are created in region 120 by laser ablation or matrixassisted laser desorption/ionization (MALDI). The ions are thenaccelerated by the ion acceleration/extraction field in region 120.

[0026] The ions are slowed in a retarding field region 150 between theextraction micro-cylinder 110 a and the middle micro-cylinder 110 b. Theretarding field region 150 serves both to collimate the ion beam, aswell as to reduce the ion velocity. The ions are then directed throughthe middle micro-cylinder 110 b, where the ions are accelerated again(up to 3 kV/mm as shown by FIG. 1B).

[0027] After traversing through the micro-cylinders 110 a-c, the ionsenter a drift region 160 within the chamber 105 where the potentialenergy is approximately 0 kV/mm as shown by the potential energy plotdepicted by FIG. 1B and referenced by numeral 160′. Reference number 170in FIG. 1B references the ion trajectories through the device 100.

[0028] The series of micro-cylinders 110 a-c minimizes losses caused byradial dispersion of ions generated during the desorption process.Although the ionization extraction device 100 of the present inventionemploys a very high extraction field 120, the ions are slowed prior toentering the drift region 160, thus resulting in longer drift times (orflight duration) and hence increased ion dispersion of the ions withinthe drift region 160.

[0029] Furthermore, the performance of the ionization extraction device100 is achieved without the use of any obstructing elements in the pathof the ions, such as grids, especially before the extractionmicro-cylinder 110 a, as in the prior art, thus eliminating transmissionlosses, signal losses due to field inhomogeneities caused by the gridwires, as well as the need for periodic grid maintenance.

[0030] B. Flexible, Circuit-Board Reflector

[0031] Ion reflectors, since their development 30 years ago, have becomea standard part in many TOF-MSs. While there have been improvements inreflector performance by modifications to the voltage gradients, themechanical fabrication is still based on stacked rings in mostlaboratory instruments. In such a design, metallic rings are stackedalong ceramic rods with insulating spacers separating each ring from thenext. While this has been proven to be satisfactory for the constructionof large reflectors, new applications of remote TOF mass analyzersrequire miniaturized components, highly ruggedized construction,lightweight materials, and the potential for mass production.

[0032] To this end, the ion reflector of the present invention shown byFIGS. 2A and 2B and designated generally by reference numeral 200 wasdeveloped utilizing the precision of printed circuit-board technologyand the physical versatility of thin, flexible substrates. A series ofthin copper traces (0.203 mm wide by 0.025 mm thick) 210 are etched ontoa flat, flexible circuit-board substrate 220 having tabs 225 protrudingfrom two opposite ends (FIG. 2B). The circuit-board substrate 220 isthen rolled into a tube 230 (FIG. 2A) to form the reflector body, withthe copper traces 210 facing inward, forming the isolated rings thatdefine the voltage gradient.

[0033] The thickness and spacing of the copper traces 210 can bemodified by simply changing the conductor pattern on the substrate sheet220 during the etching process. This feature is particularly useful forthe production of precisely tuned non-linear voltage gradients, whichare essential to parabolic or curved-field reflectors. The trace patternon the circuit-board substrate 220 shown in FIGS. 2A and 2B represents aprecision gradient in the spacing of the traces 210. Thus, in theresultant reflector, a curved potential gradient is generated byemploying resistors of equal value for the voltage divider network.

[0034] For data reported in this study (see section II), the reflectorwas constructed from a circuit-board with equally-spaced copper traces210 used in conjunction with a series of potentiometers to establish acurved potential gradient.

[0035] Once etched, the circuit-board substrate 220 is rolled around amandrel (not shown) to form a tubular shape as shown in FIG. 2A. Fivelayers of fiberglass sheets, each approximately 0.25 mm thick, are thenwrapped around the circuit-board substrate 220. The length of thecurving edge of the board 220 is approximately equal to thecircumference of the mandrel. When the sheets are wrapped around therolled circuit-board, a slight opening remains through which a connectorend 240 of the inner circuit-board can extend. The position of eachsuccessive sheet is offset slightly with respect to the previous sheetso that a gradual “ramp” is formed, thereby guiding the flexiblecircuit-board substrate 220 away from the mandrel.

[0036] The reflector assembly is heated under pressure at 150° C. forapproximately two hours, followed by removal of the mandrel. Wallthickness of the finished rolled reflector assembly is approximately 1.5mm. A multi-pin (preferably, 50-pin) ribbon-cable connector 250 issoldered onto a protruding circuit-board tab 260 so that a voltagedivider resistor network can be attached to the reflector. Alternately,soldering pads for surface-mount resistors can be designed into thecircuit-board layout, allowing the incorporation of the voltage dividernetwork directly onto the reflector assembly.

[0037] Finally, polycarbonate end cap plugs (not shown) are fitted intothe ends of the rolled reflector tube 230 to support the assembly aswell as provide a surface for affixing terminal grids. Vacuum testsindicate that the circuit-board and fiberglass assembly is compatible ofachieving vacuum levels in the low 10⁻⁷ torr range.

[0038] The reflector 200 is disclosed in a U.S. Provisional PatentApplication Serial No. 60/149,103 filed on Aug. 16, 1999 by a commonassignee as the present application.

[0039] C. Center-Hole Microchannel Plate Detector Assembly

[0040] For miniature TOF mass spectrometers, the center hole (coaxial)geometry is a highly desirable configuration because it enables thesimplification of the overall design and allows for the most compactanalyzer. However, the poor signal output characteristics ofconventional center hole microchannel plate detector assemblies,particularly the problem with signal “ringing”, clutter the baselineand, as a consequence, adversely affects the dynamic range of theinstrument. This limitation severely reduces the chance of realizinghigh performance in miniature TOF instruments, since low intensityfragment or product ion peaks can be obscured by baseline noise.Improvements to the analog signal quality of center-hole channel-platedetectors would therefore increase the ultimate performance of the massspectrometer, particularly the dynamic range.

[0041] Commercially available coaxial channel-plate detectors rely upona disk-shaped center-hole anode to collect the pulse of electronsgenerated by the microchannel plates. The anode is normally matched tothe diameter of the channel-plates, thereby, in theory, maximizing theelectron collection efficiency. However, the center-hole anode createsan extraneous capacitance within the grounded mounting enclosure. Thecenter-hole anode also produces a significant impedance mismatch whenconnected to a 50 Ω signal cable. The resultant ringing degrades andcomplicates the time-of-flight spectrum by adding a high frequencycomponent to the baseline signal. Moreover, the disk-shaped anode actsas an antenna for collecting stray high frequencies from the surroundingenvironment, such as those generated by turbo-molecular pumpcontrollers.

[0042] The pin anode design of the center-hole microchannel platedetector assembly of the present invention as shown by FIGS. 3A and 3Band designated generally by reference numeral 300 has been found tosubstantially improve the overall performance of the detector assembly300. For enhanced sensitivity, the assembly 300 includes a clamping ring305 having an entrance grid 310 which is held at ground potential whilea front surface 315 of a center-hole microchannel plate assembly 320(FIG. 3B) is set to −5 kV, post-accelerating ions to 5 keV. The clampingring 305 is bolted to an inner ring 325. The inner ring 325 is bolted toa spherical drum 330 having a tube 332 extending from a center thereofand a shield 334 encircling an outer surface 336. The tube 332 defines achannel 338. The shield is fabricated from any type of conductingmaterial, such as aluminum, and stainless steel foil.

[0043] Using voltage divider resistors, the rear of the plate assembly320 is held at 3 kV as shown by FIG. 3B. Since the collection pin anode350 is isolated from the center of the detector assembly 300, i.e.,isolated from the channel 338 defined by the tube 332, its potential isdefined by the oscilloscope's front end amplifier (nominally ground).Thus, electrons emitted from a rear microchannel plate 355 of the plateassembly 320 will be accelerated toward the grounded anode 350regardless of the anode's size, geometry, or location. The pin anode 350is located about 5 mm behind the rear microchannel plate 355.

[0044] It has been demonstrated that the pin anode 350 significantlyimproves the overall performance of the detector assembly 300. Theinventive center-hole microchannel plate detector assembly 300 virtuallyeliminates the impedance mismatch between the 50 ohm signal cable andthe electron collection surface, i.e., the pin anode 350.

[0045]FIG. 4 compares the single ion detector response for both theconventional disk anode and the pin anode configurations. It is evidentfrom FIG. 4 that ringing is significantly reduced and the ion pulsewidth is reduced to a value of 500 ps/pulse, limited by the analogbandwidth of the oscilloscope used for the measurement (1.5 GHz: 8Gsamples/sec), when using the pin anode configuration of the presentinvention. Furthermore, the background signal in the time-of-flight datacaused by spurious noise is found to be much quieter when the pin anodeconfiguration is used.

[0046] II. Results

[0047]FIG. 5 depicts a TOF-MS designated generally by reference numeral500 which has the inventive components, i.e., the focusing ionizationextraction device 100, the flexible circuit-board reflector 200, and themicrochannel plate detector assembly 300. The overall length of theentire TOF-MS is approximately 25 cm. A laser 510, such as a nitrogenlaser, is used for acquiring MALDI and laser ablation spectra. The laser510 emits a laser beam 520 which is directed through the TOF-MS 500using two mirrors 530 a, 530 b. The TOF-MS 500 is enclosed within avacuum chamber 525 and mounted into position by a bracket/rod assembly535 such that the laser beam 520 passes through a central path definedby the inventive components. In an experimental study, time-of-flightdata was acquired on a LeCroy 9384 Digital Oscilloscope (1 GHz: 2Gsam/s) used in conjunction with spectrum acquisition software.

[0048] Several different types of samples were used to test theperformance of the TOF-MS 500. Surface roughness was an importantconsideration because heavily pitted surfaces or organic samples withenlarged crystal formation can significantly increase the distributionof ion kinetic energies in the very high field extraction region.Samples were therefore prepared to ensure a smooth desorption surface.FIG. 6A displays the direct laser desorption signal obtained from aclean lead solder foil surface in which spectra from twenty consecutivelaser shots were acquired and averaged. Isotopic distributions from boththe major lead and minor tin components are clearly resolved. Peakwidths at half-maximum are approximately equal to the 5 ns laser pulsewidth (resolution m/Δm≈1000).

[0049]FIG. 6B shows the averaged MALDI spectrum (25 laser shots) ofangiotensin II using α-cyano-4-hydroxycinnamic acid as the matrix.Isotopic separation of the MH⁺ peak at 1047 Da represents a resolutionof greater than 1500.

[0050] III. Conclusions

[0051] An innovative, compact time-of-flight mass spectrometer 500 hasbeen developed using a gridless, focusing ionization extraction device100, a flexible circuit-board ion reflector 200, and a center-holemicrochannel plate detector assembly 300. Experimental studies using theTOF-MS 500 indicate that the TOF-MS 500 is capable of producing spectrawith very good resolution and low background noise; a problematicfeature of many conventional coaxial TOF-MS instruments. Results alsoindicate that background noise for data acquired on the TOF-MS 500 issubstantially reduced, resolution is improved, and the potential formass producing the TOF-MS 500 in an inexpensive and rugged package forfield-portable and remote installations is significantly enhanced.

[0052] What has been described herein is merely illustrative of theapplication of the principles of the present invention. For example, thefunctions described above and implemented as the best mode for operatingthe present invention are for illustration purposes only. Otherarrangements and methods may be implemented by those skilled in the artwithout departing from the scope and spirit of this invention.

1. A time-of-flight mass spectrometer (TOF-MS) comprising: an ionizationextraction device having an unobstructed central chamber for guidingions there through; a microchannel plate detector assembly havingchannel extending through at least a portion of the assembly; and aflexible circuit-board reflector, wherein said channel is aligned with acentral axis of said ionization extraction device and a central axis ofsaid reflector.
 2. The spectrometer according to claim 1, wherein theionization extraction device includes a first region for acceleratingions and a second region for de-accelerating the ions to collimate theions and to reduce the velocity of the ions.
 3. The spectrometeraccording to claim 2, wherein the first region creates an ionacceleration/extraction field for accelerating the ions.
 4. Thespectrometer according to claim 3, wherein the ionacceleration/extraction field created measures up to 10 kV/mm.
 5. Thespectrometer according to claim 2, wherein the ionization extractiondevice includes a third region for causing the ions to disperse and hasan electric field measurement of approximately 0 kV/mm.
 6. Thespectrometer according to claim 1, wherein the ionization extractiondevice includes a plurality of micro-cylinders mounted within thechamber for passing the ions there through from the first region to thesecond region.
 7. The spectrometer according to claim 6, wherein themicro-cylinders are metallic.
 8. The spectrometer according to claim 2,further comprising at least two regions between the first region and thesecond region, wherein the at least two regions have a differentelectric field measurement than the first region and the second region.9. An ionization extraction device for use in a TOF-MS comprising: ahousing defining an unobstructed central chamber for guiding ions therethrough; a first region within the central chamber for acceleratingions; and a second region within the central chamber in proximity to thefirst region for de-accelerating the ions entering therein.
 10. Theionization extraction device according to claim 9, wherein the firstregion creates an ion acceleration/extraction field for accelerating theions.
 11. The ionization extraction device according to claim 10,wherein the ion acceleration/extraction field created measures up to 10kV/mm.
 12. The ionization extraction device according to claim 9,further comprising a third region within the central chamber for causingthe ions to disperse and has an electric field measurement ofapproximately 0 kV/mm.
 13. The ionization extraction device according toclaim 9, further comprising a plurality of micro-cylinders mountedwithin the central chamber.
 14. The ionization extraction deviceaccording to claim 13, wherein the micro-cylinders are metallic.
 15. Theionization extraction device according to claim 9, further comprising atleast two regions between the first region and the second region,wherein the at least two regions have a different electric fieldmeasurement than the first region and the second region.
 16. A methodfor increasing the collection efficiency of laser-desorbed ions in aTOF-MS, said method comprising the steps of: providing an ionizationextraction device within the TOF-MS, the ionization extraction devicehaving an unobstructed central chamber having a first region and asecond region; creating an ion acceleration/extraction field within thefirst region; accelerating ions within the first region; de-acceleratingthe ions in the second region; and drifting the ions in a drift regionto cause ion dispersion.
 17. The method according to claim 16, whereinthe step of creating the ion acceleration/extraction field includes thestep of creating a field measuring up to 10 kV/mm.
 18. The methodaccording to claim 16, further comprising the step of creating ions inthe first region by one of laser ablation and matrix assisted laserdesorption/ionization (MALDI).
 19. The method according to claim 16,further comprising the step of aligning a central axis of the ionizationextraction device with a tubular channel of a microchannel platedetector assembly of the TOF-MS.
 20. The method according to claim 16,further comprising the step of aligning a central axis of the ionizationextraction device with a central axis of a circuit-board reflector ofthe TOF-MS.